Glia are the most abundant cells of the human nervous system, and make up about 90% of the human brain. The role of glia in support and maintenance functions in the mature nervous system is well established. More recently, new roles for glia have emerged that are central to development of the nervous system, that has a bearing on brain function and information processing. We study glia which ensheath peripheral nerves in the fruit-fly. They are generated in the embryo and undergo bouts of proliferation in the larva and later in the pupa when the adult nervous system is being re-organized. Each nerve in the Drosophila embryo is ensheathed by 3 glial layers- an innermost wrapping glial layer, the sub-perineurial layer, the perineurial layer and an extracellular matrix layer called the neural lamella. As the larva grows in size, the nerves become longer. Maintenance of nerve ensheathment occurs by proliferation of the most external layer, while the inner 2 layers increase their extensions. Studies in this proposal focus on the pupal phase when the nervous system undergoes a drastic re-organization to accommodate a new body form and behaviors. One aspect of this re-organization is the fusion of 5 pairs of posterior abdominal nerves to form a terminal nerve trunk (TNT). Our studies are aimed at understanding remodeling of (embryonically derived) peripheral glia in the context of TNT formation. We will examine how 3 distinct glial cell-types with unique functions increase in number and restructure to allow nerve fusion while keeping the blood-brain barrier intact. Individual glial layers will also be manipulatd to uncover their contribution to nerve re- organization, which results in the adult-specific patter. We hope to uncover similarities/differences between the embryonic, larval and pupal stages in regard to glial morphogenesis as it relates to nervous system structure and function. Our studies will contribute to a better understanding of human conditions such as gliomas. PUBLIC HEALTH RELEVANCE: Glial cells are the most common cell-type in the nervous system and are essential to the structure and functioning of the nervous system. We study glia which ensheath peripheral nerves in the fruit-fly. They are generated in the embryo and undergo bouts of proliferation in the larva and later in the pupa when the adult nervous system is being re- organized. Our studies will examine how 3 distinct glial cell-types with unique functions increase in number and begin the process of enstheathing the segmental nerves. We hope to uncover similarities/differences between the embryonic, larval and pupal stages in regard to glial morphogenesis as it relates to nervous system and structure. Our studies will contribute to a better understanding of human conditions such as gliomas.